Oral cancer refers to a subgroup of head and neck malignancies that develop at the lips, tongue, salivary glands, gingiva, floor of the mouth, oropharynx, buccal surfaces and other intra-oral locations, according to the International Classification of Diseases. Nevertheless, the term is synonymous to squamous cell carcinoma (SCC) of oral mucosal origin that accounts for more than 90% of all malignant presentations at the aforementioned anatomical sites. Worldwide, oral SCC (OSCC) is the sixth most common cancer; more than 300,000 new cases are diagnosed each year. The development of OSCC is a multistep process requiring the accumulation of multiple genetic alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and viral infection. The genetic changes include activation of the epidermal growth factor receptor (EGFR), alterations of tumor suppressors p53 and p16, and cyclin D1 overexpression.